PTX3-targeted Antifungal Prophylaxis

NCT03828773 | Recruiting DMC

• 1 other identifier: 2018-01671
• Study Type: interventional
• Target: 410
• Locations: 3 countries
• Sites: 9

Brief Summary

This is a prospective genetically-stratified randomized double-blind event-driven multicentre clinical trial to assess the efficacy of posaconazole-based antifungal prophylaxis allocation strategies for patients with acute myeloid leukemia who receive induction chemotherapy. Allocation strategy based on an invasive mold infection genetic risk will be double-blinded.

Conditions

Candidiasis; Fungal Infection; Acute Myeloid Leukemia; Genetic Predisposition; Aspergillosis

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence of proven and probable invasive mold infection (IMI)

  The cumulative incidence of proven and probable invasive mold infection (IMI) (based on published consensus guidelines by the EORTC/MSG groups and after validation by an independent adjudication committee of infectious disease experts blinded to treatment arms) in the intention-to-treat (ITT) population by day 180.

  Day 180

Secondary Outcomes (8)

• Cumulative incidence of possible invasive mold infection (IMI)

  Day 180

• Cumulative incidence of probable and proven Invasive Fungal Infections (IFI)

  Day 180

• Time to probable and proven invasive mold infection (IMI)

  Day 180

• Cumulative incidence of mortality

  Day 180

• Time to first use and number of patient-days of amphotericin B/echinocandin

  Day 180

Study Arms (2)

high-risk PTX3 SNPs

OTHER

risk predicted by genotyping two PTX3 single nucleotide polymorphisms (SNPs): homozygous for rs230561 and/or rs381652

Drug: Posaconazole; Drug: Fluconazole

low-risk PTX3 SNPs

OTHER

risk predicted by genotyping two PTX3 single nucleotide polymorphisms (SNPs): other than homozygous for rs230561 and/or rs381652

Drug: Posaconazole; Drug: Fluconazole

Interventions

Posaconazole DRUG

Posaconazole is a triazole with broad-spectrum activity, to include Candida species, Aspergillus species, and other fungal pathogens, including the Zygomycetes. Posaconazole is available as slow release tablets (300mg/day) and as intravenous (IV) formulation (300mg/day) and is licensed and approved in Switzerland for the prevention of IFI, including mold and yeast infections, in patients \>18 years who are at high risk of developing these types of infection (patients with long-term neutropenia or HCT recipients). Furthermore, international guidelines recommend posaconazole for primary antifungal prophylaxis in high-risk patients, such as AML patients with prolonged neutropenia. Posaconazole is available in Switzerland under the name of Noxafil® in capsules of 100mg, suspension of 40mg/mL and intravenous formulation of 300mg/16.7 mL.

Also known as: Noxafil

high-risk PTX3 SNPs; low-risk PTX3 SNPs

Fluconazole DRUG

Fluconazole is an antifungal with activity against most Candida species. Fluconazole is licensed and approved in Switzerland for prophylaxis of IC in patients with neutropenia induced by chemotherapy or radiotherapy at a daily dose of 200 to 400 mg once daily. Fluconazole (200 mg or 400 mg once daily) is still currently used as primary antifungal prophylaxis (standard of care) in all 7 centers participating in this trial. Fluconazole is available in Switzerland under the name of Diflucan® in capsules of 50 mg, 150 mg and 200 mg and in powder for preparation of suspension (50 mg/5 ml and 200 mg/5 ml (forte)) or perfusion (2 mg/1 ml). Several generics of Diflucan® are authorized in Switzerland. Prescribing Diflucan® or any of its generics will remain at the discretion of and based on the standard operating procedures (SOP) at each institution.

Also known as: Diflucan

high-risk PTX3 SNPs; low-risk PTX3 SNPs

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent according to national/local regulations.
• Age ≥18 years.
• Diagnosis of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome in transformation (MDSit) treated with an intensive chemotherapy regimen, including induction / consolidation / salvage remission chemotherapy.
• Planned hospital admission for the duration of the neutropenic phase (absolute neutrophils count \<500 cells/mm3).

You may not qualify if:

• Patients with neutropenia (absolute neutrophils count\<500 cells/mm3) upon presentation and prior to chemotherapy initiation.
• Patients with a diagnosis of acute promyelocytic leukemia (APL) or AML-M3.
• Patients with known history of allergy, hypersensitivity or serious reaction to azole antifungals
• Women who are pregnant (positive blood/urine pregnancy test within 10 days before randomization) or breast-feeding.
• Diagnosis and treatment for an Invasive Fungal Infection (IFI) within 3 months prior to study enrolment and an Invasive Mold Infection (IMI) at any point prior to or at the time of enrolment.
• Severe liver dysfunction, defined as at least one of the following markers: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) or alkaline phosphatase above \>5x upper limit of normality: and/or total bilirubin above \>3x upper limit of normality.
• Patients with an ECG with a prolonged QTc interval: QTc greater than 450 msec for men and greater than 470 msec for women.
• Patients who are receiving and cannot discontinue the following drugs at least 24 hours prior to randomization: terfenadine, astemizole, cisapride, pimozide, halofantrine or quinidine (because of the possibility of QT prolongation), sirolimus, rifampin, rifabutin, carbamazepine, long-acting barbiturates (e.g., phenobarbital, mephobarbital), ritonavir, efavirenz, or ergot alkaloids (e.g., ergotamine, dihydroergotamine).
• Serious uncontrolled concomitant disease or comorbidity that, in the opinion of the investigator, may compromise adherence to the study protocol.
• Receipt of a prior allogeneic Hematopoietic Cell Transplantation (HCT).
• Patients with relapsed leukemia already included in the trial.
• Patient not affiliated to the French social security system
• Patient under legal protection (guardianship, curatorship)

Sponsors & Collaborators

• Bochud Pierre-Yves: lead
• Swiss National Science Foundation: collaborator

Study Sites (9)

Ghent University Hospital

Ghent, Belgium, 9000, Belgium

TERMINATED

AZ Sint-Jan Hospital

Bruges, 8000, Belgium

RECRUITING

University Hospital Leuven (UZ Leuven)

Leuven, 3000, Belgium

RECRUITING

Henri Mondor Hospital

Créteil, Île-de-France Region, 94010, France

RECRUITING

Cantonal Hospital Aarau

Aarau, Aarau, 5001, Switzerland

RECRUITING

University Hospital Basel

Basel, Basel, 4031, Switzerland

RECRUITING

Cantonal Hospital HFR

Fribourg, Canton of Fribourg, 1708, Switzerland

RECRUITING

University Hospital of Geneva (HUG)

Geneva, Canton of Geneva, 1211, Switzerland

RECRUITING

University Hospital of Lausanne / Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Canton of Vaud, 1011, Switzerland

RECRUITING

MeSH Terms

Conditions

Candidiasis; Mycoses; Leukemia, Myeloid, Acute; Genetic Predisposition to Disease; Aspergillosis

Interventions

posaconazole; Fluconazole

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Pierre-Yves Bochud, MD

  Centre Hospitalier Universitaire Vaudois

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Pierre-Yves Bochud, MD

CONTACT

0041 213144379; Pierre-Yves.Bochud@chuv.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The investigational medicinal products will be known by all roles but the arm allocation based on a genetic analysis will be blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: prospective genetically-stratified randomized double-blind event-driven multicentre clinical trial

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 4, 2019
• Study Start: February 11, 2019
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-12

Locations

CH (5); BE (3); FR (1)